Crosstalk Between the Insulin-Like Growth Factors and Estrogens in Breast Cancer

Abstract

Once it was recognized that breast tumor growth was stimulated by estrogens, successfultherapeutic strategies based on depriving the tumor of this hormone were developed. Sincethe growth stimulatory properties of the estrogens are governed by the estrogen receptor (ER),4understanding the mechanisms that activate ER are highly relevant. In addition to estrogens,peptide growth factors can also activate the ER. The insulin-like growth factors (IGFs) arepotent mitogens for ER-positive breast cancer cell lines. This review will examine the evidencefor interaction between these two pathways. The IGFs can activate the ER, while ERtranscriptionally regulates genes required for IGF action. Moreover, blockade of ER function can inhibitIGF-mediated mitogenesis and interruption of IGF action can similarly inhibit estrogenicstimulation of breast cancer cells. Taken together, these observations suggest that the twogrowth regulatory pathways are tightly linked and that a further understanding of the mechanismof this crosstalk could lead to new therapeutic strategies in breast cancer.